, Volume 37, Issue 1, pp 7–18 | Cite as

Ibrutinib for Treating Waldenström’s Macroglobulinaemia: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

  • Paul TappendenEmail author
  • Christopher Carroll
  • John Stevens
  • Emma Simpson
  • Praveen Thokala
  • Ruth Wong
  • Josh Wright
  • Rebecca Auer
Review Article


As part of its Single Technology Appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of ibrutinib (Janssen) to submit evidence on the clinical and cost effectiveness of ibrutinib for treating Waldenström’s macroglobulinaemia (WM). The School of Health and Related Research Technology Assessment Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of ibrutinib based on the company’s submission to NICE. The clinical evidence was derived from one phase II, single-arm, open-label study of ibrutinib in adult patients with WM who had received at least one prior therapy (Study 1118E) and an indirect comparison using a matched cohort from a retrospective European chart review of patients receiving various treatments for WM. The indirect comparison suggested a hazard ratio for progression-free survival (PFS) of 0.25 (95% confidence interval 0.11–0.57). The ERG had concerns regarding the high risk of bias in Study 1118E, the limited generalisability of the study, and the absence of randomised controlled trial evidence. The company’s Markov model assessed the cost effectiveness of ibrutinib versus rituximab/chemotherapy for patients with relapsed/refractory (R/R) WM from the perspective of the National Health Service (NHS) and Personal Social Services (PSS) over a lifetime horizon. Based on the company’s original Patient Access Scheme (PAS), the company’s probabilistic model generated an incremental cost-effectiveness ratio (ICER) for ibrutinib versus rituximab/chemotherapy of £58,905 per quality-adjusted life-year (QALY) gained. Following a critique of the model, the ERG’s preferred analysis, which corrected cost errors and used the observed mortality rate from Study 1118E, generated a probabilistic ICER of £61,219 per QALY gained. Based on this amended model, additional exploratory analyses produced ICERs for ibrutinib that were > £60,000 per QALY gained. Subsequently, the company offered to provide ibrutinib at a price that resulted in ibrutinib being cost effective within the Cancer Drugs Fund (CDF). The Committee recommended ibrutinib for use in the CDF as an option for treating WM in adults who have had at least one prior therapy, only if the conditions in the managed access agreement for ibrutinib are followed.


Author Contributions

Christopher Carroll and Emma Simpson summarised and critiqued the clinical effectiveness data reported within the CS. Paul Tappenden and Praveen Thokala critiqued the health economic analysis submitted by the company. Ruth Wong critiqued the company’s search strategies. John Stevens critiqued the statistical analysis contained within the CS. Josh Wright and Rebecca Auer provided clinical advice to the ERG throughout the project. This summary has not been externally reviewed by PharmacoEconomics.

Compliance with Ethical Standards


This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment Programme (Project No. 15/148/03) [see the HTA programme website for further project information;]. This summary of the ERG report was compiled after NICE issued the FAD. All authors have commented on the submitted manuscript and have given their approval for the final version to be published. The views expressed in this report are those of the authors and not necessarily those of the NIHR HTA Programme. Any errors are the responsibility of the authors.

Conflicts of interest

Rebecca Auer acted as an advisor for Janssen for their submission to NICE and was paid a small advisory fee for this role. Since the completion of this appraisal, she has received a grant for a clinical trial that is anticipated to begin in November 2018. Paul Tappenden, Christopher Carroll, John Stevens, Emma Simpson, Praveen Thokala, Ruth Wong and Josh Wright declare no conflicts of interest.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.ScHARR, University of SheffieldSheffieldUK
  2. 2.Sheffield Teaching Hospitals NHS Foundation TrustSheffieldUK
  3. 3.Barts Health NHS TrustLondonUK

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